In order to determine whether cyclocytidine (Cyclo-c) captured in liposomes enhanced the effect of a single dose to the same degree as serial doses, the antitumor effect on mouse leukemia L₁₂₁₀ was examined.<BR>Cyclo-c solution (50 mg/ml) was encapsulated in the aqueous phase of neutral liposomes composed of egg lecithine and cholesterol in a 4: 3 moral ratio. The percentage of Cyclo-c taken up in the multilamellar liposomes was from 2.5% to 4.5% and was from 1.6% to 2.5% in the sonicated liposomes.<BR>The liposomally captured Cyclo-c gradually decreased by 50% on day 18 in normal saline solution under room temperature and it decreased by 50% on day 2 in the peritoneal cavities of mice.<BR>With ip administration to CDF₁ female-mice bearing ascitic L₁₂₁₀ cells, the multilamellar liposomes containing normal saline solution did not show any toxicities, antitumor activities and synergistic or antagonistic effects with free Cyclo-c. Sonicated liposomes did not show any toxicities with iv administration.<BR>Antitumor effect in mice bearing 1-day-old ascitic L₁₂₁₀ cells was judged by the percent ILS with ip, sc and iv administration of Cyclo-c or Cyclo-c liposomes. Antitumor effect in the mice bearing L₁₂₁₀ cell colonies in spleen was judged by the suppressive effect in the colony formation with ip administration of Cyclo-c or Cyclo-c liposomes. In the ip-ip experiment, the life prolongation effect of the single Cyclo- c liposome 50 mg/ kg was greater than that of the single Cyclo-c 1, 000 mg/ kg and that of the 5 consecutive doses of Cyclo-c 100 mg/kg/day. In the ip- sc and the ip-iv experiments, enhancement of the antitumor effect of a single dose of Cyclo-c liposome was also observed.<BR>The mean number of spleen colonies in the mice sacrificed 7 days after the iv injection of 1×10⁴ leukemic cells was 61. 6 (range 33-88). The mean number of spleen colonies according to different ip treatments 2 hours after the iv injection of leukemic cells was as follows: 4.7 (0-10) with the single dose of Cyclo-c 500 mg/ kg. 0 with the 5 consecutive doses of Cyclo-c 100 mg/kg/day. 14 (0-18), 2 (0-10) and 0 with the single dose of Cyclo-c liposomes 12.5 mg/kg, 25 mg/kg and 50 mg/kg, respectively.